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http://dx.doi.org/10.1038/s41375-024-02429-x | DOI Listing |
Proc Natl Acad Sci U S A
September 2025
Department of Medicine, Institute for Transformative Molecular Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106.
The β-adrenergic receptor (βAR), a prototype G protein-coupled receptor, controls cardiopulmonary function underpinning O delivery. Abundance of the βAR is canonically regulated by G protein-coupled receptor kinases and β-arrestins, but neither controls constitutive receptor levels, which are dependent on ambient O. Basal βAR expression is instead regulated by the prolyl hydroxylase/pVHL-E3 ubiquitin ligase system, explaining O responsivity.
View Article and Find Full Text PDFLeukemia
September 2025
Department of Hematology of First Affiliated Hospital, and Department of Public Health, Zhejiang University School of Medicine, Hangzhou, China.
BCR::ABL1 oncofusion protein drives Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL), making it a critical therapeutic target. Tyrosine kinase inhibitors (TKIs) targeting BCR::ABL1 have revolutionized the treatment of Ph+ ALL patients. However, mutations in the kinase domain of BCR::ABL1 commonly impair the sensitivity to TKIs, resulting in drug resistance and poor prognosis in Ph+ ALL.
View Article and Find Full Text PDFLeukemia
March 2025
Department of Translational Hematology & Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, 44114, USA.
J Pediatr Hematol Oncol
August 2021
Department of Pathology and Laboratory Medicine.
The diagnostic criteria for juvenile myelomonocytic leukemia have recently been revised to include clinical findings and RAS-pathway gene mutations per the 2016 World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues. Differing clinical behaviors have been observed in cases with CBL versus other RAS-pathway gene (RAS-p) mutations, notably the patients with CBL mutations can be self-limiting with spontaneous resolution. Additional clinical characteristics and histopathologic findings between these subsets are less well-described.
View Article and Find Full Text PDFJ Mol Biol
April 2021
The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Program in Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Medical Biophysics, University of T
CBL is a RING type E3 ubiquitin ligase that functions as a negative regulator of tyrosine kinase signaling and loss of CBL E3 function is implicated in several forms of leukemia. The Src-like adaptor proteins (SLAP/SLAP2) bind to CBL and are required for CBL-dependent downregulation of antigen receptor, cytokine receptor, and receptor tyrosine kinase signaling. Despite the established role of SLAP/SLAP2 in regulating CBL activity, the nature of the interaction and the mechanisms involved are not known.
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